Source Citation

Abstract

Objective

To investigate the effect of early thrombolytic therapy with recombinant tissue-type
plasminogen activator (rt-PA) on the analgesic needs of patients with myocardial infarction.

Design

Substudy of the randomized, double-blind, placebo-controlled trial of early thrombolytic
therapy (Anglo-Scandinavian Study of Early Thrombolysis-ASSET), with analgesics given
as needed. Analgesic requirements were assessed during the first 48 hours of thrombolytic
therapy.

Setting

4 Danish centers.

Patients

76 of 129 patients < 76 years of age (range, 37 to 75 y) with suspected myocardial
infarction of < 5 hours duration had the infarction confirmed by enzymatic or
electrocardiographic changes (or both) and were permitted analgesics on demand. Patients
who were prescribed intravenous nitroglycerine, β-blockers, or naloxone were excluded.
3 patients randomized to rt-PA and 6 randomized to placebo were excluded because they
required nitroglycerine. Of 67 patients, 43 were men.

Intervention

Patients were treated with 100 mg of intravenous rt-PA (n = 30) or placebo (n = 37) within 5 hours of the myocardial infarction. All patients received intravenously
injected heparin, 5000 IU, followed by an infusion of 1000 IU/h for 21 hours. Analgesics
(morphinomimetics or levomepromazine, with dosage converted into equivalents of mg
of morphine) were given at the patient's request or when the nurses observed the patient
to be in pain.

Main outcome measure

Total analgesic requirements during the 48-hour period after starting thrombolysis
or placebo.

Main results

Patients assigned to rt-PA required a median of 5.3 mg of morphine (range, 0 to 45
mg) in 48 hours, compared with a median of 11.2 mg (range, 0 to 115 mg) for the placebo
group (P = 0.04). 20 of 30 patients (67%) receiving rt-PA did not require analgesics for >
6 hours compared with 14 of 37 patients (38%) assigned to placebo (P = 0.04). {This absolute risk improvement of 28% means that 3 patients would need to
be treated with rt-PA (compared with placebo) to have 1 additional patient not require
analgesics for > 6 hours, 95% CI 2 to 21, the relative risk improvement was 76%,
CI 10% to 192%}.*

Conclusion

Administration of rt-PA within 5 hours after myocardial infarction reduced the total
analgesic requirements of patients in the next 48 hours. Compared with a control group,
fewer patients on the rt-PA regimen required analgesia for more than 6 hours.

Commentary

The authors of this substudy have shown that the early use of rt-PA reduces the requirements
for analgesia within the first 48 hours. The blinded nature of the study should have
minimized biases in the administration of analgesia. Although the total amount and
duration of analgesia were lower with rt-PA after the start of therapy, no data were
provided on the analgesic requirements from time of presentation to the onset of thrombolysis.
It is possible that early imbalances in the use of analgesics may have accounted for
these results. Patients excluded were those receiving either β-blockers or intravenous
nitrates, preventing their potential confounding effects on the pain of acute myocardial
infarction.

The implication of these results is that thrombolysis reduces the pain of acute myocardial
infarction, probably (but not certainly) caused by reperfusion. A comparison of several
different thrombolytic agents might give indirect evidence for this hypothesis because
different agents produce differing velocities of reperfusion, although patency rates
appear to be similar at 24 hours.

These results are based on the differences between group medians, but the overall
care of the individual patient with a suspected acute myocardial infarction need not
differ because of the use of thrombolytic agents. It is important that physicians
not get caught up in the excitement of using these extremely effective agents and
inadvertently forget the other essential aspects of the management and care of the
patient, including pain control.